Calcineurin

Calcineurin is a Ca²⁺/calmodulin-dependent serine/threonine protein phosphatase that plays a critical role in immune regulation, neural signal transmission, cardiovascular modulation, and cell apoptosis. One of its most important functions is dephosphorylating NFAT (nuclear factor of activated T cells), promoting its nuclear translocation and thereby regulating T cell activation and immune response. Additionally, Calcineurin modulates synaptic plasticity (by influencing the AMPA/NMDA receptor pathway), cardiac hypertrophy (via NFAT and CaMKII pathways regulating cardiomyocyte growth), and cell survival and apoptosis (through Bcl-2 and FasL-related signaling pathways). Calcineurin is widely studied in organ transplant rejection prevention and autoimmune disease research.
Calcineurin has three major isoforms:
CNAα: Primarily expressed in immune cells (T and B cells), neural tissues, and the heart, where it participates in immune regulation, neural signaling, and cardiovascular control.
CNAβ: Widely distributed in most tissues, with high expression in the skeletal muscle, liver, and pancreas, playing roles in metabolic regulation and cell proliferation.
CNAγ: Mainly expressed in the testes, potentially associated with spermatogenesis and male reproductive function.
Calcineurin is implicated in various diseases, including autoimmune diseases (psoriasis, rheumatoid arthritis), neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease), cardiovascular diseases (hypertension, cardiac hypertrophy), and cancers (T-cell lymphoma, breast cancer). Overactivation of Calcineurin may lead to excessive immune responses, neural damage, and cardiomyopathy, whereas its inhibition could result in immune deficiency, osteoporosis, and kidney damage^[1].

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